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1.
Low Carbohydrate Diets and Estimated Cardiovascular and Metabolic Syndrome Risk in Prostate Cancer.
Freedland, SJ, Howard, LE, Ngo, A, Ramirez-Torres, A, Csizmadi, I, Cheng, S, Mack, A, Lin, PH
The Journal of urology. 2021;(6):1411-1419
Abstract
PURPOSE A low carbohydrate diet (LCD) was shown to suggestively slow prostate cancer (PC) growth. In noncancer patients, LCDs improve metabolic syndrome (MetS) without weight loss. However, concerns about negative impact on cardiovascular disease (CVD) risk remain. The objective of this secondary analysis is to determine the impact of an LCD on risk of MetS and estimated CVD risk in patients with PC. MATERIALS AND METHODS Pooled data were analyzed from 2 randomized trials testing LCD vs control on 1) preventing insulin resistance after starting hormone therapy (CAPS1) and 2) slowing PC growth in recurrent PC after failed primary treatment (CAPS2). Both trials included a usual care control vs LCD intervention in which patients were instructed to limit carbohydrate intake to ≤20 gm/day, and in CAPS1 only, to walk for ≥30 minutes/day for ≥5 days/week. MetS components (hypertension, high triglycerides, low high-density lipoprotein cholesterol, central obesity and diabetes), 10-year CVD risk estimated using the Framingham Score with either body mass index (BMI) or lipids, and remnant cholesterol were compared between arms using mixed models adjusting for trial. RESULTS LCD resulted in a significantly reduced risk of MetS (p=0.004) and remnant cholesterol (p <0.001). Moreover, LCD resulted in significantly lower estimated CVD risk using BMI (p=0.002) over the study with no difference in estimated CVD risk using lipids (p=0.14). CONCLUSIONS LCD resulted in a significantly reduced risk of MetS and remnant cholesterol, and a significantly lower estimated CVD risk using BMI. By comparison, there was no difference in estimated CVD risk using lipids. Study limitations include small sample size, short followup, and inability to distinguish effects of carbohydrate restriction and weight loss. Long-term studies are needed to confirm this finding.
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2.
Adverse effects of androgen deprivation therapy in patients with prostate cancer: Focus on muscle and bone health.
Bargiota, A, Oeconomou, A, Zachos, I, Samarinas, M, L Pisters, L, Tzortzis, V
Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2020;(3):1286-1294
Abstract
Androgen deprivation therapy (ADT) is the most effective systemic treatment for prostate cancer and can be succeeded either surgically or pharmaceutically. Both approaches lead to hypogonadism with a large variety of adverse events, including obesity, metabolic syndrome, osteoporosis, sarcopenia, diabetes mellitus, cardiovascular disease, gynecomastia and sexual dysfunction. In addition, undesirable effects on muscle and bone health may have a significant impact not only on the quality of life but also on life expectancy. Currently, supervised exercise seems to be the only intervention that could prevent the adverse effects of the ADT and improve quality of life. Lifestyle modification, supplementation of calcium, vitamin D and when indicated antiosteoporotic treatments improve bone health. However, patients receiving ADT must be well informed about the potential benefits as well as the risks of the treatment.
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3.
Primary Care of the Prostate Cancer Survivor.
Noonan, EM, Farrell, TW
American family physician. 2016;(9):764-70
Abstract
This summary of the American Cancer Society Prostate Cancer Survivorship Care Guidelines targets primary care physicians who coordinate care of prostate cancer survivors with subspecialists. Prostate cancer survivors should undergo prostate-specific antigen screening every six to 12 months and digital rectal examination annually. Surveillance of patients who choose watchful waiting for their prostate cancer should be conducted by a subspecialist. Any hematuria or rectal bleeding must be thoroughly evaluated. Prostate cancer survivors should be screened regularly for urinary incontinence and sexual dysfunction. Patients with predominant urge incontinence symptoms, which can occur after surgical and radiation treatments, may benefit from an anticholinergic agent. If there is difficulty with bladder emptying, a trial of an alpha blocker may be considered. A phosphodiesterase type 5 inhibitor can effectively treat sexual dysfunction following treatment for prostate cancer. Osteoporosis screening should occur before initiation of androgen deprivation therapy, and patients treated with androgen deprivation therapy should be monitored for anemia, metabolic syndrome, and vasomotor symptoms. Healthy lifestyle choices should be encouraged, including weight management, regular physical activity, proper nutrition, and smoking cessation. Primary care physicians should be vigilant for psychosocial distress, including depression, among prostate cancer survivors, as well as the potential impact of this distress on patients' family members and partners.
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4.
Adverse effects of androgen deprivation therapy and strategies to mitigate them.
Nguyen, PL, Alibhai, SM, Basaria, S, D'Amico, AV, Kantoff, PW, Keating, NL, Penson, DF, Rosario, DJ, Tombal, B, Smith, MR
European urology. 2015;(5):825-36
Abstract
CONTEXT Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition. OBJECTIVE To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. EVIDENCE ACQUISITION The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. EVIDENCE SYNTHESIS Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). CONCLUSIONS ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. PATIENT SUMMARY Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.
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5.
Metabolic effects of androgen deprivation therapy.
Choi, SM, Kam, SC
Korean journal of urology. 2015;(1):12-8
Abstract
The therapeutic effects and side effects of androgen deprivation therapy (ADT), which is a main treatment method for metastatic prostate cancer, are well known, but the metabolic effects have only recently been studied. This review describes the effects of ADT on body habitus, insulin resistance, lipid profiles, diabetes, metabolic syndrome, and cardiovascular morbidity and mortality. The review was done by using KoreaMed and PubMed to search the medical literature related to prostate cancer, ADT, body habitus, lipid profile, diabetes, insulin resistance, metabolic syndrome, and cardiovascular disease. ADT increases fat mass and decreases lean body mass. Fat mostly accumulates in the subcutaneous area. ADT increases total cholesterol, triglycerides, and high-density lipoprotein, as well as the risk for insulin resistance and diabetes. ADT also increases the risk for cardiovascular events, but insufficient evidence is available for a correlation with mortality. ADT changes body habitus and lipid profiles and has different characteristics than those of classic metabolic syndrome, but it is related to insulin resistance and diabetes. ADT increases the risk for cardiovascular events. No consistent guidelines have been proposed for treating the metabolic effects of ADT, but the generally recommended treatment methods for lowering the risk of diabetes and cardiovascular disease should be fully understood. Additional studies are necessary.
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6.
The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy.
Morote, J, Gómez-Caamaño, A, Alvarez-Ossorio, JL, Pesqueira, D, Tabernero, A, Gómez Veiga, F, Lorente, JA, Porras, M, Lobato, JJ, Ribal, MJ, et al
The Journal of urology. 2015;(6):1963-9
Abstract
PURPOSE Androgen deprivation therapy may promote the development of the metabolic syndrome in patients with prostate cancer. We assessed the prevalence of the full metabolic syndrome and its components during the first year of androgen deprivation therapy. MATERIALS AND METHODS This observational, multicenter, prospective study included 539 patients with prostate cancer scheduled to receive 3-month depot luteinizing hormone-releasing hormone analogs for more than 12 months. Waist circumference, body mass index, lipid profile, blood pressure and fasting glucose were evaluated at baseline and after 6 and 12 months. The metabolic syndrome was assessed according to NCEP ATP III criteria (2001) and 4 other definitions (WHO 1998, AACE 2003, AHA/NHLBI 2005 and IDF 2005). RESULTS At 6 and 12 months after the initiation of androgen deprivation therapy, significant increases were observed in waist circumference, body mass index, fasting glucose, triglycerides, total cholesterol, and high-density and low-density lipoprotein cholesterol. No significant changes in blood pressure 130/85 or greater were detected. A nonsignificant increase of 3.9% in the prevalence of the full metabolic syndrome (ATP III) was observed (22.9% at baseline vs 25.5% and 26.8% at 6 and 12 months, respectively). The prevalence of the metabolic syndrome at baseline varied according to the definition used, ranging from 9.4% (WHO) to 50% (IDF). At 12 months significant increases in prevalence were observed with the WHO (4.1%) and AHA/NHLBI (8.1%) definitions. CONCLUSIONS Androgen deprivation therapy produces significant early effects on waist circumference, body mass index, fasting glucose, triglycerides and cholesterol. The prevalence of and increase in the metabolic syndrome depend on the defining criteria. Counseling patients on the prevention, early detection and treatment of specific metabolic alterations is recommended.
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7.
Metabolic complications of androgen deprivation therapy for prostate cancer.
Saylor, PJ, Smith, MR
The Journal of urology. 2013;(1 Suppl):S34-42; discussion S43-4
Abstract
PURPOSE Androgen deprivation therapy has a variety of well recognized adverse effects including vasomotor flushing, loss of libido, fatigue, gynecomastia, anemia and osteoporosis. This review focuses on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease. MATERIALS AND METHODS We reviewed the medical literature using the PubMed® search terms prostate cancer, androgen deprivation therapy, gonadotropin-releasing hormone agonists, obesity, insulin resistance, lipids, diabetes, cardiovascular disease and myocardial infarction. We provide a focused review and our perspective on the relevant literature. RESULTS Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol. CONCLUSIONS Androgen deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms. Little is known about the optimal strategy to mitigate the adverse metabolic effects of androgen deprivation therapy. Thus, we recommend an emphasis on existing strategies for screening and treatment that have been documented to reduce the risk of diabetes and cardiovascular disease in the general population.
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8.
Prostate cancer and metabolic syndrome: is there a link?
McGrowder, DA, Jackson, LA, Crawford, TV
Asian Pacific journal of cancer prevention : APJCP. 2012;(1):1-13
Abstract
Metabolic syndrome has become quite prevalent within our society. Over the past two decades, the prevalence of metabolic syndrome has sharply increased worldwide and it has become a major public health problem in several countries. It is associated with the global epidemic of obesity and diabetes mellitus and imposes numerous cardiovascular risks. Prostate cancer is the second most common cancer among men, surpassed only by non-melanoma skin cancer. A considerable body of evidence exists suggesting that some components of the metabolic syndrome have been associated with the risk of prostate cancer. These components include obesity, an abdominal fat distribution, and hyperinsulinemia. Androgen deprivation therapy (ADT) is the most widely used therapeutic modality in prostate cancer. It changed the body composition and lipid profile of men with prostate cancer. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein (LDL)- cholesterol, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. The aim of this review is to evaluate the association between metabolic syndrome and prostate cancer and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. A comprehensive literature search was carried out with the use of PubMed from 1980 through 2012, and relevant articles pertinent to metabolic syndrome and prostate cancer are evaluated and discussed.
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9.
High-dose isoflavones do not improve metabolic and inflammatory parameters in androgen-deprived men with prostate cancer.
Napora, JK, Short, RG, Muller, DC, Carlson, OD, Odetunde, JO, Xu, X, Carducci, M, Travison, TG, Maggio, M, Egan, JM, et al
Journal of andrology. 2011;(1):40-8
Abstract
The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for prostate cancer (PCa) results in complications such as diabetes and metabolic syndrome that predispose to cardiovascular disease. Because phytoestrogens have been associated with an improvement in metabolic parameters, we evaluated their role in men undergoing ADT. Our objective was to evaluate the effects of high-dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT. This was a randomized, double-blind, placebo-controlled, 12-week pilot study. Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The study was conducted at a tertiary care center in the United States. Thirty-three men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot study. Mean age in the 2 groups was 69 years and the majority of men were Caucasians. Mean duration of ADT in both groups was approximately 2 years (P = .70). The 2 groups were well matched at baseline. After 12 weeks of intervention, there was no significant difference in either metabolic or inflammatory parameters between the 2 groups. We found that high-dose isoflavones over a course of 12 weeks do not improve metabolic or inflammatory parameters in androgen-deprived men.
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10.
Emerging cardiometabolic complications of androgen deprivation therapy.
Choong, K, Basaria, S
The aging male : the official journal of the International Society for the Study of the Aging Male. 2010;(1):1-9
Abstract
Prostate cancer (PCa) is the most common malignancy in men. Androgen deprivation therapy (ADT) is used in the treatment of locally advanced and metastatic PCa. Although its use has improved survival in a subset of patients, it also has negative consequences. Osteoporosis, sexual dysfunction, hot flashes and adverse changes in body composition are well-known and well-studied complications of ADT. Recent studies have also found metabolic complications in these men such as insulin resistance, diabetes and metabolic syndrome. In addition, these men might also experience higher cardiovascular mortality. Studies are needed to determine the mechanism behind these complications and to employ strategies to prevent them.